The Correlation of Tumour Budding and Epithelial-Mesenchymal Transition Associated with The Prognosis of Oral Squamous Carcinoma- A Systematic Review

Abstract

Oral squamous cell carcinoma (OSCC) is a prevalent and aggressive cancer that arises from the epithelial cells found in the oral cavity. Despite advances in diagnosis and treatment, its prognosis remains poor due to its high potential for local invasion and metastasis. Prognostic outcomes are influenced by factors such as tumor size and stage, lymph node involvement, patient demographics, lifestyle habits, histological grade, tumor margins, perineural and lymphovascular invasion, tumor budding, and molecular markers like E-cadherin and p16. Among these, tumor budding, characterized by solitary individual cells or small clusters at the invasive edge, serves as a significant predictor of lymph node metastasis and signifies aggressive tumor behavior. It has already been acknowledged as an important prognostic factor in various cancers, such as colorectal, esophageal, and lung cancers. Tumor budding is believed to represent the epithelial-mesenchymal transition (EMT), a biological process in which epithelial cells gain mesenchymal characteristics, allowing them to separate, migrate, and invade adjacent tissues. During EMT, cells lose polarity and adhesion molecules such as E-cadherin while gaining mesenchymal markers like vimentin and fibronectin. This transformation enhances tumor aggressiveness and is linked to increased mortality. Tumor buds frequently exhibit features associated with epithelial-mesenchymal transition (EMT), such as the activation of the WNT/β-catenin signaling pathway and the downregulation of E-cadherin. While these observations indicate a significant link between tumor budding and EMT, the precise nature of their relationship in oral squamous cell carcinoma (OSCC) has yet to be completely clarified.